This COBRE Phase III proposal aims to further develop the Center for Molecular Medicine at the University of Kentucky. This Center focuses on research aimed at understanding the molecular mechanisms associated with human disease with emphases on cancer, neurodegenerative diseases, diabetes, and cardiovascular diseases. We propose to transition to independence the research infrastructure developed during previous COBRE funding. Our COBRE funded Center for Molecular Medicine has had a number of successes. During the previous funding period 30 junior faculty from 12 different departments and centers were funded as COBRE project or pilot grant PIs. These mentored faculty received 27 NIH ROI grants, 11 other NIH grants, and 41 other peer-reviewed extramural grants. The COBRE-supported junior faculty published more than 400 research papers. These and other successes can in large part be attributed to a strong mentoring program, excellent institutional support, and the availability of the scientific cores associated with the Center. For this application, we propose to transition the Center for Molecular Medicine and its three scientific cores to independence of NIH/NIGMS support and to enhance and upgrade core technologies. It is worth noting that two of our original cores have or soon will transition to independence; the Proteomics core developed by this COBRE is now a University fee-for-service core, and the COBRE supported Imaging core is soon to become a department supported core. During the proposed five-year transition period we will increase the critical mass of faculty associated with the Center and continue to enhace its Cores. The use of vouchers will promote core usage and pilot grants will develop research collaborations and competitive grant submissions. The Administrative Core will serve as the focal point of the grant and in conjunction with the Program Coordinator and Internal Advisory Committee will serve as the operational arm of the Center. An External Advisory Committee, consisting of world-renown scientists will provide ongoing assessment and evaluation of the Center. Continuing Institutional commitments will ensure programmatic growth, and long-term sustainability.